Chapter 25
Nitrogen Acquisition and
Amino Acid Metabolism
Biochemistry
by
Reginald Garrett and Charles Grisham
Outline
1. Which Metabolic Pathways Allow Organisms
to Live on Inorganic Forms of Nitrogen?
2. What Is The Metabolic Fate of Ammonium?
3. What Regulatory Mechanisms Act on
Escherichia coli Glutamine Synthetase?
4. How Do Organisms Synthesize Amino
Acids?
5. How Does Amino Acid Catabolism Lead into
Pathways of Energy Production?
25.1 – Which Metabolic Pathways
Allow Organisms to Live on
Inorganic Forms of Nitrogen?
Nitrogen is cycled between organisms and
inanimate enviroment
• The principal inorganic forms of N are in an
oxidized state
– As N2 in the atmosphere
– As nitrate (NO3-) in the soils and ocean
• All biological compounds contain N in a
reduced form (NH4+)
• Thus, Nitrogen acquisition must involve
1. The Reduction of the oxidized forms (N2 and NO3-)
to NH4+
2. The incorporation of NH4+ into organic linkage as
amino or amido groups
• The reduction occurs in microorganisms and
green plants. But animals gain N through diet.
(+3)
(-3)
(+5)
(-3)
(+5)
(+2)
(+3)
(+1)
(0)
Figure 25.1 The
nitrogen cycle.
The Reduction of Nitrogen
Nitrogen assimilation and nitrogen fixation
1. Nitrate assimilation occurs in two steps:
–
–
•
2e- reduction of nitrate to nitrite
6e- reduction of nitrite to ammonium (Fig 25.1)
Nitrate assimilation accounts for 99% of N
acquisition by the biosphere
2. Nitrogen fixation involves reduction of N2 in
prokaryotes by nitrogenase
Nitrate Assimilation
•
Nitrate assimilation
–
the reduction of nitrate to NH4+ in plants,
various fungi, and certain bacteria
– Two steps:
1. Nitrate reductase
NO3- + 2 H+ + 2 e- → NO2- + H2O
2. Nitrite reductase
NO2- + 8 H+ + 6 e- → NH4+ + 2 H2O
•
Electrons are transferred from NADH to
nitrate
Nitrate reductase
•
Nitrate reductases are cytosolic 210-270 kD
dimeric protein, pathway involve
–
–
–
–
•
SH of enzyme
FAD
Cytochrome b557
Molybdenum cofactor
MoCo required both for reductase activity and
for assembly of enzyme subunits to active dimer
NO3-
NADH
[E-SH →FAD→cytochrome b557 →MoCo]
NAD+
NO2-
Nitrite Reductase
Light drives reduction of ferredoxins and
electrons flow to 4Fe-4S and siroheme and
then to nitrite
• Nitrite is reduced to ammonium
while still bound to siroheme
• In higher plants, nitrite reductase
is in chloroplasts, but nitrate
reductase is cytosolic
In higher plants
siroheme
Figure 25.3 Domain organization within the enzymes of nitrate assimilation. The
numbers denote residue number along the amino acid sequence of the proteins.
Nitrogen fixation
•
N2 + 10 H+ + 8 e- → 2 NH4+ + H2
Only occurs in certain prokaryotes
–
–
•
Rhizobia fix nitrogen in symbiotic association
with leguminous plants
Rhizobia fix N for the plant and plant provides
Rhizobia with carbon substrates
Fundamental requirements:
1.
2.
3.
4.
Nitrogenase
A strong reductant (reduced ferredoxin)
ATP
O-free conditions
Nitrogenase Complex
Two metalloprotein components:
1. Nitrogenase reductase
2. Nitrogenase
Nitrogenase reductase
• Nitrogenase reductase
– Fe-protein
– A 60 kD homodimer with a single 4Fe-4S cluster
• Extremely O2-sensitive
• Binds MgATP and hydrolyzes 2 ATPs per
electron transferred
• Because reduction of N2 to 2NH4+ + H2 requires
8 electrons, 16 ATP are consumed per N2
reduced
Figure 25.4 The triple
bond in N2 must be broken
during nitrogen fixation.
• N2 reduction to ammonia is thermodynamically favorable
• However, the activation barrier for breaking the N-N triple
bond is enormous
• 16 ATP provide the needed activation energy
Nitrogenase
•
•
MoFe-protein—a 220 kD a2b2 heterotetramer
An ab-dimer serve as the functional unit
– Contains two types of metal centers
1. P-cluster (figure 25.5a)
8Fe-7S center
2. FeMo-cofactor (figure 25.5b)
7Fe-1-Mo-9S cluster
•
•
Oxygen labile
Nitrogenase is a rather slow enzyme
– 12 e- pairs per second, i.e., only three molecules of N2
per second
– As much as 5% of cellular protein may be nitrogenase
Figure 25.5 Structures of the two
types of metal clusters found in
nitrogenase.
(a) The P-cluster consists of two
Fe4S3 clusters that share an S
atom. (8Fe-7S)
(b) The FeMo-cofactor contains 1
Mo, 7Fe, and 9S atoms.
Homocitrate provides two oxo
ligands to the Mo atom.
The regulation of nitrogen Fixation
• Two regulatory controls
1. ADP inhibits the activity of
nitrogenase
2. NH4+ represses the
expression of nif genes
• In some organisms, the
nitrogenase complex is
regulated by covalent
modification. ADPribosylation of nitrogenase
reductase leads to its
inactivation.
Figure 25.8
Regulation of
nitrogen
fixation.
25.2 – What Is The Metabolic Fate of
Ammonium?
NH4+ enters organic linkage via three major
reactions in all cells
1.
2.
3.
•
Glutamate dehydrogenase (GDH)
Glutamine synthetase (GS)
Carbamoyl-phosphate synthetase I (CPS-I)
Asparagine synthetase (some
microorganisms)
1. Glutamate dehydrogenase (GDH)
•
Reductive amination of a-ketoglutarate to
form glutamate
NH4+ + a-ketoglutarate + NADPH + 2 H+ →
glutamate + NADP+ + H2O
• Mammalian GDH plays a prominent role in amino
acid catabolism (oxidative amination)
2. Glutamine synthetase (GS)
•
ATP-dependent amidation of g-carboxyl of
glutamate to glutamine
NH4+ + glutamate + ATP →
glutamine + ADP + Pi
•
•
Glutamine is a major N donor in the
biosynthesis of many organic N compounds,
therefore GS activity is tightly regulated
Glutamine is the most abundant amino acid in
human
Figure 25.10
(a) The enzymatic
reaction catalyzed by
glutamine synthetase.
(b) The reaction
proceeds by (a)
activation of the gcarboxyl group of Glu by
ATP, followed by (b)
amidation by NH4+.
3. Carbamoyl-phosphate synthetase I (CPS-I)
Ammonium is converted to carbamoyl-P
•
This reaction is an early step in the urea
cycle
NH4+ + HCO3- + 2 ATP →
carbamoyl phosphate + 2 ADP + Pi + 2 H+
•
Two ATP required
– one to activate bicarbonate
– one to phosphorylate carbamate
The major pathways of Ammonium
Assimilation lead to glutamin synthesis
Two principal pathways :
1. Principal route: GDH/GS in organisms rich in N
2. Secondary route: GS/GOGAT in organisms
confronting N limitation
– GOGAT is glutamate synthase or glutamate:oxoglutarate amino transferase
– GDH has a higher Km for NH4+ than does GS
The glutamate synthase (GOGAT)reaction, showing the reductants exploited
by different organisms in this reductive amination reaction.
25.3 – What Regulatory Mechanisms
Act on Glutamine Synthetase
•
GS in E. coli is regulated in three ways:
1. Feedback inhibition (allosteric regulation)
2. Covalent modification (interconverts between
inactive and active forms)
3. Regulation of gene expression and protein
synthesis control the amount of GS in cells
•
•
But no such regulation occurs in eukaryotic
versions of GS
E. coli GS is a
12-mer
1. Allosteric Regulation of Glutamine
Synthetase
• 9 different feedback inhibitors: Gly, Ala, Ser, His,
Trp, CTP, AMP, carbamoyl-P, and glucosamine-6-P
– Gly, Ala, Ser are indicators of amino acid metabolism in
cells
– Other six are end products of a biochemical pathway
• AMP competes with ATP for binding at the ATP
substrate site
• Gly, Ala, and Ser compete with Glu for binding at
the active site
• This effectively controls glutamine’s contributions to
metabolism
Figure 25.15 The allosteric regulation
of glutamine synthetase activity by
feedback inhibition.
2. Covalent Modification of
Glutamine Synthetase
• Each subunit can be adenylylated at Tyr-397
– Adenylylation inactivates GS
• ATP:GS:adenylyl transferase (AT) catalyzes both the
adenylylation and deadenylylation
– PII (regulatory protein) controls these
– AT:PIIA catalyzes adenylylation
– AT:PIID (PII-UMP) catalyzes deadenylylation
• a-Ketoglutarate and Gln also affect
– a-Ketoglutarate activates AT:PIID and inhibit AT:PIIA
– Gln activates AT:PIIA and inhibit AT:PIID
Figure 25.16 Covalent modification of GS: Adenylylation of Tyr397 in
the glutamine synthetase polypeptide via an ATP-dependent reaction
catalyzed by the converter enzyme adenylyl transferase (AT).
From 1 through 12 GS monomers in the GS holoenzyme can be modified, with
progressive inactivation as the ratio of [modified]/[unmodified] GS subunits
increases.
(Adenylylation)
(Deadenylylation)
Figure 25.17 The cyclic cascade system
regulating the covalent modification of GS.
3. Gene Expression regulates GS
Gene GlnA is actively transcribed only if a
transcriptional enhancer NRI is in its
phosphorylated form, NRI-P
• NRI is phosphorylated by
NRII, a protein kinase
• If NRII is complexed with
PIIA it acts as a phosphatase,
not a kinase
(kinase)
(phosphatase)
25.4 – Amino Acid Biosynthesis
• Organisms show substantial differences in their
capacity to synthesize the 20 amino acids
common to proteins
– Plants and microorganisms can make all 20 amino
acids and all other needed N metabolites
– In these organisms, glutamate is the source of N, via
transamination (aminotransferase) reactions
• Amino acids are formed from a-keto acids by
transamination
Amino acid1 + a-keto acid2 → a-keto acid1 + Amino acid2
Figure 25.19 Glutamate-dependent transamination of a-keto acid carbon
skeletons is a primary mechanism for amino acid synthesis.
The Mechanism of the Aminotransferase (Transamination) Reaction
*Arginine and
histidine are
essential in the
diets of juveniles,
not adults
• Mammals can make only 10 of the 20 AAs
– The others are classed as "essential" amino acids and
must be obtained in the diet
The pathways of amino acid biosynthesis
can be organized into families
According to the intermediates that they are
made from
1. a-ketoglutarate
2. Oxaloacetate
3. Pytuvate
4. 3-phosphoglycerate
5. Phosphoenolpyruvate and erythrose-4-P (aromatic)
1. The a-Ketoglutarate Family
Glu, Gln, Pro, Arg, and sometimes Lys
• The routes for Glu and Gln synthesis were
described when we considered pathways of
ammonia assimilation
– Transamination of a-Ketoglutarate gives glutamate
– Amidation of glutamate gives glutamine
• Proline is derived from glutamate
• Ornithine is also derived from glutamate
– the similarity to the proline pathway
• Arginine are part of the urea cycle
Figure 25.20 The pathway of proline biosynthesis from glutamate. The enzymes are (1) gglutamyl kinase, (2) glutamate-5-semialdehyde dehydrogenase, and (4) D1-pyrroline-5carboxylate reductase; reaction (3) occurs nonenzymatically.
(1) N-acetylglutamate synthase
(3) N-acetylglutamate-5-semialdehyde
dehydrogenase
(4) N-acetylornithine d-aminotransferase
(5) N-acetylornithine deacetylase
(2) N-acetylglutamate
kinase
•
Ornithine has three metabolic roles
1. To serve as precursor to arginine
2. To function as an intermediate in the urea cycle
3. To act as an intermediate in arginine degradation
•
d-NH3+ of ornithine is carbamoylated by
onithine transcarbamoylase in urea cycle
Carbamoyl-phosphate synthetase I
•
Carbamoyl-phosphate synthetase I (CPS-I)
–
NH3-dependent mitochondrial CPS isozyme
1. HCO3- is activated via an ATP-dependent
phosphorylation
2. Ammonia attacks the carbonyl carbon of
carbonyl-P, displacing Pi to form carbamate
3. Carbamate is phosphorylated via a second ATP
to give carbamoyl-P
Figure 25.22 The mechanism of action of CPS-I
•
CPS-I represents the committed step in urea
cycle
•
Activated by N-acetylglutamate
–
Because N-acetylglutamate is a precursor to
orinithine synthesis and essential to the
operation of the urea cycle

amino acid catabolism ↑

glutamate level (N-acetylglutamate) ↑

Stimulate CPS-I

Raise overall Urea cycle activity
1. Ornithine
transcarbamoylase
(OTCase)
2. Argininosuccinate
synthetase
Urea Cycle
4. Arginase
3. Argininosuccinase
The Urea Cycle
• The carbon skeleton of arginine is derived
from a-ketoglutarate (Ornithine)
• N and C in the guanidino group of Arg
come from NH4+, HCO3- (carbamoyl-P), and
the a-NH2 of Glu and Asp
• Breakdown of Arg in the urea cycle releases
two N and one C as urea
• Important N excretion mechanism in livers
of terrestrial vertebrates
• Urea cycle is linked to TCA by fumarate
Lysine Biosynthesis
•
Two pathways:
1. a-aminoadipate pathway
2. diaminopimelate pathway (Asp)
•
Lysine derived from a-ketoglutarate
–
–
•
•
•
•
Reactions 1 through 4 are reminiscent of the first four
reactions in the citric acid cycle
a-ketooadipate
Transamination gives a-aminoadipate
Adenylylation activates the d-COOH for reduction
Reductive amination give saccharopine
Oxidative cleavage yields lysine
Figure 25.24 Lysine biosynthesis in certain
fungi and Euglena: the a-aminoadipic acid
pathway.
2. The Aspartate Family
Asp, Asn, Lys, Met, Thr, Ile
• Transamination of Oxaloaceate gives Aspartate
(aspartate aminotransferase)
• Amidation of Asp gives Asparagine ( asparagine
synthetase)
• Met, Thr and Lys are made from Aspartate
– b-Aspartyl semialdehyde and homoserine are branch
points
• Isoleucine, four of its six carbons derived from
Asp (via Thr) and two come from pyruvate
Figure 25.25 Aspartate biosynthesis via transamination of
oxaloacetate by glutamate.
Figure 25.26 Asparagine
biosynthesis from Asp, Gln, and ATP
by asparagine synthetase.
Figure 25.27 Biosynthesis
of threonine, methionine, and
lysine, members of the
aspartate family of amino
acids.
b-Aspartyl-semialdehyde is a
common precursor to all
three.
It is formed by aspartokinase
(reaction 1) and b-aspartylsemialdehyde dehydrogenase
(reaction 2).
Figure 25.27 Biosynthesis of threonine, methionine, and lysine,
members of the aspartate family of amino acids.
Figure 25.27 Biosynthesis of threonine, methionine, and
lysine, members of the aspartate family of amino acids.
b-Aspartyl-semialdehyde
Figure 25.27 Biosynthesis of
threonine, methionine, and
lysine, members of the
aspartate family of amino acids.
In E. coli, The first reaction is an ATP-dependent
phosphorylation catalyzed by aspartokinase
– Three isozymes of aspartokinase (I, II, and III)
– Uniquely controlled by one of the three endproducts
– Form I is feedback-inhibited by threonine
– Form III is feedback-inhibited by lysine
Important role of
methionine
• in methylations via Sadenosylmethionine
(SAM; S-AdoMet)
• polyamine
biosynthesis
Figure 25.28 The synthesis
of S-adenosylmethionine
(SAM)
3. The Pyruvate Family
Ala, Val, Leu, and Ile
• Transamination of pyruvate gives Alanine
• Valine is derived from pyruvate
• Ile synthesis from Thr mimics Val synthesis
from pyruvate (Fig. 25.29)
– Threonine deaminase (also called threonine
dehydratase or serine dehydratase) is sensitive to Ile
– Ile and val pathway employ the same set of enzymes
• Leu synthesis begins with an a-keto isovalerate
– Isopropylmalate synthase is sensitive to Leu
Figure 25.29 Biosynthesis of
valine and isoleucine.
Threonine
deaminase
Isopropylmalate
synthase
HydroxyethylthiaminePP
Acetohydroxy acid synthase
Isopropylmalate
dehydratase
Acetohydroxy acid
isomeroreductase
Isopropylmalate
dehydrogenase
Dihydroxy acid
dehydratase
Leucine
aminotransferase
Glutamate-dependent
aminotransferase
4. 3-Phosphoglycerate Family
Ser, Gly, Cys
1. 3-Phosphoglycerate dehydrogenase
diverts 3-PG from glycolysis to
amino acid synthesis pathways (3phosphohydroxypyruvate)
2. Transamination by Glu gives 3phosphoserine (3-phosphoserine
aminotransferase)
3. Phosphoserine phosphatase yields
serine
•
Serine hydroxymethylase (PLP-dependent) transfers
the b-carbon of Ser to THF to make glycine
Figure 25.32 Biosynthesis of
glycine from serine (a) via serine
hydroxymethyltransferase and (b)
via glycine oxidase.
•
A PLP-dependent enzyme makes Cys
Some bacteria
most microorganism and plants
O-acetylserine sulfhydrylase
serine acetyltransferase
Figure 25.33 Cysteine biosynthesis. (a) Direct sulfhydrylation of serine by H2S.
(b) H2S-dependent sulfhydrylation of O-acetylserine.
ATP sulfurylase
Adenosine-5'-phosphosulfate-3'-phosphokinase.
Figure 25.34 Sulfate assimilation and
the generation of sulfide for synthesis
of organic S compounds.
Sulfite oxidase
5. Aromatic Amino Acids
Phe, Tyr, Trp, His
• The aromatic amino acids, Phe, Tyr, and
Trp, are derived from shikimate pathway
yields chorismate, thence Phe, Tyr, Trp
• Chorismate as a branch point in this pathway
(Figs. 25.35)
– Chorismate is synthesized from PEP and
erythrose-4-P
– Via shikimate pathway
– The side chain of chorismate is derived from a
second PEP
Figure 25.35 Some of the
aromatic compounds derived
from chorismate.
(1) 2-keto-3-deoxy-D-arabino-heptulosonate-7-P synthase
(2) dehydroquinate synthase
(3) 5-dehydroquinate dehydratase
(4) shikimate dehydrogenase
(5) shikimate kinase
(6) 3-enolpyruvyl-shikimate-5-phosphate synthase
(7) chorismate synthase.
The Biosynthesis of Phe, Tyr, and Trp
• At chorismate, the pathway separates into
three branches, each leading to one of the
aromatic amino acids
• Mammals can synthesize tyrosine from
phenylalanine by phenylalanine hydroxylase
(Phenylalanine-4-monooxygenase)
Figure 25.38 The
formation of tyrosine
from phenylalanine.
Figure 25.37 The biosynthesis of
phenylalanine, tyrosine, and
tryptophan from chorismate.
(1) chorismate mutase
(2) prephenate dehydratase
(3) phenylalanine aminotransferase
(4) prephenate dehydrogenase
(5) tyrosine aminotransferase
(6) anthranilate synthase
(7) anthranilate-phosphoribosyl
transferase
(8) N-(5'-phosphoribosyl)anthranilate isomerase
(9) indole-3-glycerol phosphate
synthase
(10) tryptophan synthase (a-subunit)
(11) tryptophan synthase (bsubunit).
Histidine Biosynthesis
• His synthesis, like that of Trp, shares
metabolic intermediates (PRPP) with purine
biosynthetic pathway
• His operon
• Begin from PRPP and ATP
• The intermediate 5-aminoimidazole-4carboxamide ribonucleotide (AICAR) is a
purine precursor (replenish ATP; Ch 26)
Figure 25.40 The pathway of
histidine biosynthesis.
(1) ATP-phosphoribosyl
transferase
(2) pyrophosphohydrolase
(3) phosphoribosyl-AMP
cyclohydrolase
(4) phosphoribosylformimino-5aminoimidazole carboxamide
ribonucleotide isomerase
(5) glutamine amidotransferase
(6) imidazole glycerol-P
dehydratase
(7) L-histidinol phosphate
aminotransferase
(8) histidinol phosphate
phosphatase
(9) histidinol dehydrogenase.
Amino Acid Biosynthesis Inhibitors as
Herbicides
A variety of herbicides have been developed as
inhibitors of plant enzymes that synthesize
“essential” amino acids
• These substances show no effect on animals
• For example, glyphosate, sold as RoundUp, is a
PEP analog that acts as an uncompetitive
inhibitor of 3-enolpyruvylshikimate-5-P
synthase.
Amino acid synthesis inhibitors as herbicides
(inhibitor of 3-enolpyruvyl-shikimate-5phosphate synthase)
(fig 25.36)
(inhibitor of acetohydroxy acid synthase in biosynthesis
of valine and isoleucine) (fig 25.29)
(inhibitor of imidazol glycerol-P dehydrtase
in biosynthesis of histidine) (fig 25.40)
(inhibitor of glutamine synthetase)
25.5 – Degradation of Amino Acids
The 20 amino acids are degraded to produce
(mostly) TCA intermediates
• The primary physiological purpose of amino
acids is to serve as building blocks for protein
synthesis
• Energy requirement
– 90% from oxidation of carbohydrates and fats
– 10% from oxidation of amino acids
• The classifications of amino acids in Fig. 25.41
• Glucogenic and ketogenic
Figure 25.41 Metabolic degradation of the
common amino acids. Glucogenic amino
acids are shown in pink, ketogenic in blue.
Those that give rise to precursors
for glucose synthesis, such as
a-ketoglutarate,
succinyl-CoA,
fumarate,
oxaloacetate, and
pyruvate, are termed glucogenic
(shown in pink).
Those degraded to acetyl-CoA or
acetoacetate are called ketogenic
(shown in blue) because they can
be converted to fatty acids or
ketone bodies.
Some amino acids are both
glucogenic and ketogenic.
The 20 amino acids are degraded by 20
different pathways that converge to just 7
metabolic intermediates
C-3 family (pyruvate):
Ala, Ser, Cys, Gly, Thr, Trp
C-4 family (oxaloaceate & fumarate):
Oxaloaceate: Asp, Asn
Fumarate: Asp, Phe, Tyr
C-5 family (a-ketoglutarate):
Glu, Gln, Arg, Pro, His
Succinyl-CoA:
Ile, Met, Val
Acetyl-CoA & acetoacetate
Ile, Leu, Thr, Trp
Leu, Lys, Phe, Tyr
C-3 family:
Ala, Ser, Cys, Gly, Thr, Trp
Figure 25.42 Formation of pyruvate
from alanine, serine, cysteine,
glycine, tryptophan, or threonine.
Figure 25.43 The degradation of the C-5
family of amino acids leads to aketoglutarate via glutamate. The
histidine carbons, numbered 1 through 5,
become carbons 1 through 5 of glutamate,
as indicated.
Figure 25.44 Valine, isoleucine,
and methionine are converted via
propionyl-CoA to succinyl-CoA
for entry into the citric acid cycle.
The shaded carbon atoms of the
three amino acids give rise to
propionyl-CoA.
All three amino acids lose their
a-carboxyl group as CO2.
Methionine first becomes Sadenosylmethionine, then
homocysteine (see Figure 25.28).
The terminal two carbons of
isoleucine become acetyl-CoA.
Leucine is Degraded to Acetyl-CoA and
Acetoacetate
Figure 25.45 Leucine is one of only two purely ketogenic amino acids; the other
is lysine.
Deamination of leucine via a transamination reaction yields α-ketoisocaproate,
which is oxidatively decarboxylated to isovaleryl-CoA. Subsequent reactions give
β-hydroxy-β-methylglutaryl-CoA, which is then cleaved to yield acetyl-CoA and
acetoacetate, a ketone body.
Hereditary defects in
BCKDH leads to maple
sugar urine disease
Unlike the other 17 amino
acids, which are broken
down in the liver, Val, Ile,
and Leu are also degraded
in adipose tissue.
The Predominant Pathway of Lysine Degradation
is the Saccharopine Pathway
Figure 25.47 Lysine is degraded through saccharopine and α-aminoadipate to αketoadipate. Oxidative decarboxylation yields glutaryl-CoA, which can be
transformed into acetoacetyl-CoA and then acetoacetate.
Phenylalanine and Tyrosine Are Degraded
to Acetoacetate and Fumarate
• The first reaction in phenylalanine degradation is the
hydroxylation reaction of tyrosine biosynthesis
• Both these amino acids thus share a common
degradative pathway
• Transamination of tyrosine yields phydroxyphenylpyruvate
• A vitamin C-dependent dioxygenase then produces
homogentisate
• Ring opening and isomerization gives 4-fumarylacetoacetate, which is hydrolyzed to acetoacetate and
fumarate
Figure 25.48 Phenylalanine and tyrosine degradation.
(1) Transamination of Tyr gives p-hydroxyphenylpyruvate
(2) p-hydroxy-phenylpyruvate dioxygenase (vitamin C-dependent)
(3) homogentisate dioxygenase
(4) 4-Maleylacetoacetate isomerase
(5) is hydrolyzed by fumarylacetoacetase.
Tryptophan is a crucial precusor
for synthesis of a variety of
important substances
•Serotonin (5-hydroxytryptophan)
is a neurotransmitter
•Melatonin (N-acetyl-5methoxytrptophan) is a hormone
Hereditary defects
Maple syrup urine disease
– After the initial step (deamination) to produce a-keto
acids
– The defect in oxidative decarboxylation of Ile, Leu,
and Val (25.44)
Phenylketonuria
– The defect in phenylalanine hydoxylase (25.38)
– Accumulation of phenylpyruvate
Alkaptouria
– Homogentisate dioxygenase (25.47)
Nitrogen excretion
Ammonotelic:
– Ammonia
– Aquatic animals
Ureotelic:
– Urea
– Terrestrial vetebrates
Uricotelic:
– Uric acid
– Birds and reptiles